PUBLICATION
A duplication on chromosome 16q12 affecting the IRXB gene cluster is associated with autosomal dominant cone dystrophy with early tritanopic color vision defect
- Authors
- Kohl, S., Llavona, P., Sauer, A., Reuter, P., Weisschuh, N., Kempf, M., Dehmelt, F.A., Arrenberg, A.B., Sliesoraityte, I., Zrenner, E., van Schooneveld, M.J., Rudolph, G., Kühlewein, L., Wissinger, B.
- ID
- ZDB-PUB-210424-8
- Date
- 2021
- Source
- Human molecular genetics 30(13): 1218-1229 (Journal)
- Registered Authors
- Arrenberg, Aristides
- Keywords
- none
- MeSH Terms
-
- Gene Expression Regulation
- Female
- Pedigree
- Animals
- Homeodomain Proteins/genetics*
- Zebrafish/genetics
- Chromosome Duplication*
- Family Health
- Color Vision Defects/genetics*
- Genes, Dominant/genetics
- Chromosomes, Human, Pair 16/genetics*
- Transcription Factors/genetics*
- Multigene Family*
- Sequence Analysis, DNA/methods
- Humans
- Cone Dystrophy/genetics*
- Comparative Genomic Hybridization/methods
- Male
- PubMed
- 33891002 Full text @ Hum. Mol. Genet.
Citation
Kohl, S., Llavona, P., Sauer, A., Reuter, P., Weisschuh, N., Kempf, M., Dehmelt, F.A., Arrenberg, A.B., Sliesoraityte, I., Zrenner, E., van Schooneveld, M.J., Rudolph, G., Kühlewein, L., Wissinger, B. (2021) A duplication on chromosome 16q12 affecting the IRXB gene cluster is associated with autosomal dominant cone dystrophy with early tritanopic color vision defect. Human molecular genetics. 30(13):1218-1229.
Abstract
Cone dystrophies are a rare subgroup of inherited retinal dystrophies and hallmarked by color vision defects, low or decreasing visual acuity and central vision loss, nystagmus and photophobia. Applying genome-wide linkage analysis and array comparative genome hybridization, we identified a locus for autosomal dominant cone dystrophy on chromosome 16q12 in four independent multi-generation families. The locus is defined by duplications of variable size with a smallest region of overlap of 608 kb affecting the IRXB gene cluster, and encompasses the genes IRX5 and IRX6. IRX5 and IRX6 belong to the Iroquois (Iro) protein family of homeodomain-containing transcription factors involved in patterning and regionalization of embryonic tissue in vertebrates, including the eye and the retina. All patients presented with a unique progressive cone dystrophy phenotype hallmarked by early tritanopic color vision defects. We propose that the disease underlies a misregulation of the IRXB gene cluster on chromosome 16q12, and demonstrate that overexpression of Irx5a and Irx6a, the two orthologous genes in zebrafish, results in visual impairment in 5-day old zebrafish larvae.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping